Current status of the development of intravesical drug delivery systems for the treatment of bladder cancer

ABSTRACT

Introduction

Intravesical instillation is preferred over the systemic route of administration, as an efficient route of drug administration to treat bladder cancer. However, the periodic voiding of urine washes out the instilled drugs, eventually resulting in reduced drug exposure. Moreover, the presence of the bladder permeability barrier limits drug permeation into tumor tissues. It is therefore important to develop a novel delivery system that not only promotes prolonged retention of drugs in the bladder but also enables drugs to penetrate the barrier.

Areas covered

This review addresses the limitations of conventional therapeutic regimens and reports the use of polymeric hydrogels and nano/microcarriers for enhanced intravesical drug delivery in bladder cancer. Strategies to prolong residence time in the bladder and enhance cell penetration and target-cell specificity are discussed.

Expert opinion

Although promising results have been obtained in the field of intravesical drug delivery, numerous questions remain unanswered in terms of therapeutic efficacy. Specialized function covering extended drug exposure and/or enhanced drug uptake should be considered. Assessment protocols that adequately mimic the human bladder environment in vitro and in vivo experiments are needed to expedite formulation development.

KEYWORDS:

• Bladder cancer
• bladder retention
• cell uptake
• hydrogel
• intravesical drug delivery
• nanocarrier
• target ligand

Article highlights

• The use of polymeric hydrogels is a major development in the field of intravesical drug-delivery systems that enables prolonged residence time in the bladder and ultimately eliminates the need for frequent administration.

• Thermo-reversible gels allow temperature-mediated sol–gel transition and facilitate sustained drug release in the bladder.

• Mucoadhesion via electrostatic interaction and/or thiol modification enhances the intimate contact between the delivery system and the bladder wall and subsequently increases drug uptake.

• Intravesical delivery systems can be further enhanced with the concept of floating to avoid urinary obstruction and/or the use of nanoparticles to facilitate drug delivery.

• Nanocarriers can be functionalized with various ligands to impart target-cell specificity and enhance drug uptake into cancer cells.

This box summarizes key points contained in the article.

Acknowledgments

We would like to thank Editage (www.editage.co.kr) for English language editing (CAUNE_5943).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was funded by the Ministry of Health and Welfare, Republic of Korea, through the Korea Health Industry Development Institute (KHIDI; HI17C0710) and was supported by a National Research Foundation of Korea (NRF) grant, funded by the Korea government (MSIT; 2019R1A2C2002510).